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A prompt diagnosis of urinary tract infection (UTI) is necessary to minimize its symptoms and limit sequelae. The current UTI screening by urine test strip analysis and microscopic examination has suboptimal diagnostic accuracy. A definitive diagnosis of UTI by urine culture takes two to three days for the results. These limitations necessitate a need for better biomarkers for the diagnosis and subsequent management of UTI in children. Here, we review the value of currently available UTI biomarkers and highlight the potential of emerging biomarkers that can facilitate a more rapid and accurate UTI diagnosis. Of the newer UTI biomarkers, the most promising are blood procalcitonin (PCT) and urinary neutrophil gelatinase-associated lipocalin (NGAL). PCT can provide diagnostic benefits and should be considered in patients who have a blood test for other reasons. NGAL, which is on the threshold of clinical care, needs more research to address its scope and utilization, including point-of-care application. Employment of these and other biomarkers may ultimately improve UTI diagnosis, guide UTI therapy, reduce antibiotic use, and mitigate UTI complications. [ABSTRACT FROM AUTHOR]

Urinary tract infection (UTI) commonly afflicts people with diabetes. This augmented infection risk is partly due to deregulated insulin receptor (IR) signaling in the kidney collecting duct. The collecting duct is composed of intercalated cells (ICs) and principal cells (PCs). Evidence suggests that ICs contribute to UTI defenses. Here, we interrogate how IR deletion in ICs impacts antibacterial defenses against uropathogenic Escherichia coli. We also explore how IR deletion affects immune responses in neighboring PCs with intact IR expression. To accomplish this objective, we profile the transcriptomes of IC and PC populations enriched from kidneys of wild-type and IC-specific IR knock-out mice that have increased UTI susceptibility. Transcriptomic analysis demonstrates that IR deletion suppresses IC-integrated stress responses and innate immune defenses. To define how IR shapes these immune defenses, we employ murine and human kidney cultures. When challenged with bacteria, murine ICs and human kidney cells with deregulated IR signaling cannot engage central components of the integrated stress response--including activating transcriptional factor 4 (ATF4). Silencing ATF4 impairs NFkB activation and promotes infection. In turn, NFkB silencing augments infection and suppresses antimicrobial peptide expression. In diabetic mice and people with diabetes, collecting duct cells show reduced IR expression, impaired integrated stress response engagement, and compromised immunity. Collectively, these translational data illustrate how IR orchestrates collecting duct antibacterial responses and the communication between ICs and PCs. [ABSTRACT FROM AUTHOR]

Semiochemicals can be used to manipulate insect behaviour for sustainable pest management strategies, but their high volatility is a major issue for their practical implementation. Inclusion of these molecules within porous materials is a potential solution to this issue, as it can allow for a slower and more controlled release. In this work, we demonstrate that a series of Zr(IV) and Al(III) metal‐organic frameworks (MOFs) with channel‐type pores enable controlled release of three semiochemicals over 100 days by pore size design, with the uptake and rate of release highly dependent on the pore size. Insight from grand canonical Monte Carlo simulations indicates that this is due to weaker MOF‐guest interactions per guest molecule as the pore size increases. These MOFs are all stable post‐release and can be reloaded to show near‐identical re‐release profiles. These results provide valuable insight on the diffusion behaviour of volatile guests in MOFs, and for the further development of porous materials for sustainable agriculture applications. [ABSTRACT FROM AUTHOR]

Caregiver-infant interactions shape infants' early visual experience; however, there is limited work from low-and middle-income countries (LMIC) in characterizing the visual cognitive dynamics of these interactions. Here, we present an innovative dyadic visual cognition pipeline using machine learning methods which captures, processes, and analyses the visual dynamics of caregiver-infant interactions across cultures. We undertake two studies to examine its application in both low (rural India) and high (urban UK) resource settings. Study 1 develops and validates the pipeline to process caregiver-infant interaction data captured using head-mounted cameras and eye-trackers. We use face detection and object recognition networks and validate these tools using 12 caregiver-infant dyads (4 dyads froma 6-month-old UK cohort, 4 dyads froma 6-month-old India cohort, and 4 dyads froma 9-month-old India cohort). Results show robust and accurate face and toy detection, as well as a high percent agreement between processed andmanually coded dyadic interactions. Study 2 applied the pipeline to a larger data set (25 6-month-olds from the UK, 31 6-month-olds from India, and 37 9-month-olds from India) with the aim of comparing the visual dynamics of caregiver-infant interaction across the two cultural settings. Results show remarkable correspondence between key measures of visual exploration across cultures, including longer mean look durations during infant-led joint attention episodes. In addition, we found several differences across cultures. Most notably, infants in the UK had a higher proportion of infant-led joint attention episodes consistent with a child-centered view of parenting common in western middle-class families. In summary, the pipeline we report provides an objective assessment tool to quantify the visual dynamics of caregiver-infant interaction across high- and low-resource settings. [ABSTRACT FROM AUTHOR]

The Lucy mission is NASA’s 13th Discovery-class mission and the first mission to the Trojan asteroids. The spacecraft conducts flybys of 8 Trojan asteroids over the course of 12 years. A series of 3 Earth Gravity Assists are used to increase the aphelion of the spacecraft’s orbit and to target the final Trojan asteroid flyby. Over the course of 2 years the spacecraft conducts 4 flybys in the L4 swarm to explore 6 Trojan asteroids, which includes two small satellites. Near the end of the mission, Lucy flies past the near-equal size binary, Patroclus-Menoetius, in the L5 swarm. The concept of operations for the Trojan flybys invokes a standard timeline for spacecraft operations to allow a science sequence that is tailored to each Trojan asteroid. The concept of operations enables efficiency of observations and resiliency in the observing sequence to robustly meet the Lucy science requirements. [ABSTRACT FROM AUTHOR]

The Europa Thermal Emission Imaging System (E-THEMIS) on the Europa Clipper spacecraft will investigate the temperature and physical properties of Europa using thermal infrared (TIR) images in three wavelength bands centered from 7-14 μm, 14-28 μm and 28-80 μm. E-THEMIS will map >80% of the surface Europa at multiple times of day at a resolution of 8-km per pixel, ∼32% percent of the surface at ≤1 km/pixel resolution, and ∼6% percent at ≤100 m/pixel resolution. The specific objectives of the investigation are to 1) understand the formation of surface features, including sites of recent or current geologic activity, in order to understand regional and global processes and evolution and 2) to identify safe sites for future landed missions. E-THEMIS uses an uncooled microbolometer detector array for the IR focal plane. The E-THEMIS focal plane has 920 cross-track pixels (896 active) and 140 along-track pixels in each of the three spectral bands. The image data are collected at 14-bits per pixel at a frame rate of 60 Hz. The instrument can operate in framing mode, where full frame images are collected, and optionally co-added in time, in each band, or in time-delay-integration (TDI) mode where consecutive rows from each band are offset spatially to remove the spacecraft motion and then summed. In addition, the data in each band can be spatially aggregated from 2 × 2 to 5 × 5 pixels. These modes will be varied throughout each Europa flyby to optimize the data precision while fitting within the E-THEMIS data allocation. The expected temperature precision, measured as the noise equivalent spectral radiance, is 1.2 K at scene temperatures ≥90 K for a TDI of 16 with 4 × 4 pixel coaggregation in Band 2. The absolute accuracy at 90 K is 2−3 K in Band 2. E-THEMIS is an all-reflective, three-mirror anastigmat telescope with a 6.45-cm effective aperture and a speed of f/1.34 cross-track and 1.92 along-track. The mass of instrument Sensor Assembly, mounted on the spacecraft nadir deck, is 11.4 kg, the vault electronics are 1.8 kg, and the two are connected through a 3.1 kg harness. The Sensor volume is 23.7 cm x 31.8 cm x 29.8 cm. E-THEMIS consumes an average operation power of 34.8 W at 28 V. E-THEMIS was developed by Arizona State University with Raytheon Vision Systems developing the microbolometer focal plane assembly and Ball Aerospace developing the electronics. E-THEMIS was integrated, tested, and radiometrically calibrated on the Arizona State University campus in Tempe, AZ. [ABSTRACT FROM AUTHOR]

Asteroids with diameters less than about 5 km have complex histories because they are small enough for radiative torques (that is, YORP, short for the Yarkovsky–O’Keefe–Radzievskii–Paddack effect)1 to be a notable factor in their evolution2. (152830) Dinkinesh is a small asteroid orbiting the Sun near the inner edge of the main asteroid belt with a heliocentric semimajor axis of 2.19 au; its S-type spectrum3,4 is typical of bodies in this part of the main belt5. Here we report observations by the Lucy spacecraft6,7 as it passed within 431 km of Dinkinesh. Lucy revealed Dinkinesh, which has an effective diameter of only 720 m, to be unexpectedly complex. Of particular note is the presence of a prominent longitudinal trough overlain by a substantial equatorial ridge and the discovery of the first confirmed contact binary satellite, now named (152830) Dinkinesh I Selam. Selam consists of two near-equal-sized lobes with diameters of 210 m and 230 m. It orbits Dinkinesh at a distance of 3.1 km with an orbital period of about 52.7 h and is tidally locked. The dynamical state, angular momentum and geomorphologic observations of the system lead us to infer that the ridge and trough of Dinkinesh are probably the result of mass failure resulting from spin-up by YORP followed by the partial reaccretion of the shed material. Selam probably accreted from material shed by this event.Observations from the Lucy spacecraft of the small main-belt asteroid (152830) Dinkinesh reveals unexpected complexity, with a longitudinal trough and equatorial ridge, as well as the discovery of the first contact binary satellite. [ABSTRACT FROM AUTHOR]

The Lucy spacecraft successfully performed the first of two Earth Gravity Assist maneuvers on October 16th 2022, flying 360 km above the Earth's surface at 11:04 UT. The flyby was essential for the Lucy mission design, but also provided a wealth of data for scientific, calibration, and public engagement purposes. The Earth and Moon provided excellent calibration targets, being large, bright, and well-characterized, though instrument saturation was sometimes an issue, as the instruments are designed for operation 5 AU from the sun. Calibration data of the Earth and/or Moon were taken with all Lucy instruments, improving knowledge of instrument alignment, stray light characteristics, and sensitivity to resolved targets. In addition, Lucy obtained scientifically valuable thermal emission spectra of the Moon, and extensive images of the DART mission impact into the Didymos system, from a unique geometry, 20 days before the Earth flyby. [ABSTRACT FROM AUTHOR]

We present two cases of cricoid chondronecrosis treated with hyperbaric oxygen (HBO2) therapy. Both patients presented with biphasic stridor and dyspnea several weeks after an intubation event. Tracheostomy was ultimately performed for airway protection, followed by antibiotic treatment and outpatient HBO2 therapy. Both patients were decannulated within six months of presentation and after at least 20 HBO2 therapy sessions. Despite a small sample size, our findings are consistent with data supporting HBO2 therapy's effects on tissue edema, neovascularization, and HBO2 potentiation of antibiotic treatment and leukocyte function. We suggest HBO2 therapy may have accelerated airway decannulation by way of infection resolution as well as the revitalization of upper airway tissues, ultimately renewing the structural integrity of the larynx. When presented with this rare but significant clinical challenge, physicians should be aware of the potential benefits of HBO2 therapy. [ABSTRACT FROM AUTHOR]

The interaction of visual exploration and auditory processing is central to early cognitive development, supporting object discrimination, categorization, and word learning. Research has shown visual–auditory interactions to be complex, created from multiple processes and changing over multiple timescales. To better understand these interactions, we generalize a formal neural process model of early word learning to two studies examining how words impact 9‐ to 22‐month‐olds' attention to novelty. These simulations clarify the origin and nature of previously demonstrated effects of labels on visual exploration and the basis of mutual exclusivity effects in word learning. We use our findings to discuss key questions for this special section: what makes a good theory and how should formal theories interface with empirical paradigms and findings? [ABSTRACT FROM AUTHOR]

Objectives: The prospective cohort design is an important research design, but a common challenge is missing data. The purpose of this study is to compare three approaches to managing missing data, the pairwise (n = 1386 children), the partial or modified pairwise (n = 1019) and the listwise (n = 546), to characterize the trajectories of children's free sugars intake (FSI) across early childhood. Methods: By applying the Group‐based Trajectory Model Technique to three waves of data collected from a prospective cohort study of South Australian children, this study examined the three approaches in managing missing data to validate and discuss children's FSI trajectories. Results: Each approach identified three distinct trajectories of child's FSI from 1 to 5 years of age: (1) 'low and fast increasing', (2) 'moderate and increasing' and (3) 'high and increasing'. The trajectory memberships were consistent across the three approaches, and were for the pairwise scenario (1) 15.1%, (2) 68.3% and (3) 16.6%; the partial or modified pairwise (1) 15.9%, (2) 64.1% and (3) 20.0%; and the listwise (1) 14.9%, (2) 64.9% and (3) 20.2% of children. Conclusions: Given the comparability of the findings across the analytical approaches and the samples' characteristics between baseline and across different data collection waves, it is recommended that the pairwise approach be used in future analyses to optimize the sample size and statistical power when examining the relationship between FSI in the first years of life and health outcome such as dental caries. [ABSTRACT FROM AUTHOR]

The use of artemisinin and its derivatives has helped reduce the burden of malaria caused by Plasmodium falciparum. However, artemisinin-resistant parasites are able, in the presence of artemisinins, to stop their cell cycles. This quiescent state can alter the activity of artemisinin partner drugs leading to a secondary drug resistance and thus threatens malaria eradication strategies. Drugs targeting epigenetic mechanisms (namely epidrugs) are emerging as potential antimalarial drugs. Here, we set out to evaluate a selection of various epidrugs for their activity against quiescent parasites, to explore the possibility of using these compounds to counter artemisinin resistance. The 32 chosen epidrugs were first screened for their antiplasmodial activity and selectivity. We then demonstrated, thanks to the specific Quiescent-stage Survival Assay, that four epidrugs targeting both histone methylation or deacetylation as well as DNA methylation decrease the ability of artemisinin-resistant parasites to recover after artemisinin exposure. In the quest for novel antiplasmodial drugs with new modes of action, these results reinforce the therapeutic potential of epidrugs as antiplasmodial drugs especially in the context of artemisinin resistance. [ABSTRACT FROM AUTHOR]

Main Belt asteroid (152830) Dinkinesh will be the first fly-by target of the Lucy mission on 2023 November 1, during its cruise to the Trojan clouds. We report our photometric time series observations of this target performed on 14 nights over nearly three months during the 2022-23 apparition with the 1.23-m telescope at Calar Alto, Spain, aimed at determining its rotation and photometric properties. We find that Dinkinesh is a slow rotator (P syn = 52.67 ± 0.04 h) with a moderately large light-curve amplitude (A  = 0.39 ± 0.02), which implies an axial ratio a / b ≳ 1.43. Its photometric parameters in the HG-system are H R = 17.17 ± 0.04 and G R = 0.378 ± 0.035 with a colour index |$\rm {V \!-\! R}$|  = 0.455 ± 0.025. A fit to the IAU |$\rm {H,G_1,G_2}$| system results in |$H_{\rm R-(H,G_1,G_2)}$|  = 17.17 ± 0.14; G 1  = 0.37 ± 0.17 and G 2  = 0.43 ± 0.04. Assuming that Dinkinesh's albedo lies within ±2σ of the average value for small S-class asteroids, its spherical surface-equivalent diameter is between 0.66 and 1.36 km. [ABSTRACT FROM AUTHOR]

Functional changes in chaperone systems play a major role in the decline of cognition and contribute to neurological pathologies, such as Alzheimer's disease (AD). While such a decline may occur naturally with age or with stress or trauma, the mechanisms involved have remained elusive. The current models suggest that amyloid-β (Aβ) plaque formation leads to the hyperphosphorylation of tau by a Hsp90-dependent process that triggers tau neurofibrillary tangle formation and neurotoxicity. Several co-chaperones of Hsp90 can influence the phosphorylation of tau, including FKBP51, FKBP52 and PP5. In particular, elevated levels of FKBP51 occur with age and stress and are further elevated in AD. Recently, the dihydropyridine LA1011 was shown to reduce tau pathology and amyloid plaque formation in transgenic AD mice, probably through its interaction with Hsp90, although the precise mode of action is currently unknown. Here, we present a co-crystal structure of LA1011 in complex with a fragment of Hsp90. We show that LA1011 can disrupt the binding of FKBP51, which might help to rebalance the Hsp90-FKBP51 chaperone machinery and provide a favourable prognosis towards AD. However, without direct evidence, we cannot completely rule out effects on other Hsp90-co-chaprone complexes and the mechanisms they are involved in, including effects on Hsp90 client proteins. Nonetheless, it is highly significant that LA1011 showed promise in our previous AD mouse models, as AD is generally a disease affecting older patients, where slowing of disease progression could result in AD no longer being life limiting. The clinical value of LA1011 and its possible derivatives thereof remains to be seen. [ABSTRACT FROM AUTHOR]

Background: Fluid overload leads to poor neonatal outcomes. Diuretics may lower the rates of mechanical ventilation (MV) and mortality in neonates with fluid overload. Methods: This is a retrospective study of preterm neonates ≤ 36 weeks of gestational age (GA) in the first 14 postnatal days in a level IV NICU in 2014–2020. We evaluated the epidemiology of fluid balance in the first 14 postnatal days and its association with MV and mortality and studied the association of diuretics with fluid balance, MV, and mortality. Results: In 1383 included neonates, the overall median lowest and peak fluid balances were − 7.8% (IQR: − 11.7, − 4.6) and 8% (3, 16) on days 3 (2, 5) and 13 (5, 14), respectively. Fluid balance distribution varied significantly by GA. Peak fluid balance of ≥ 10% was associated with increased odds of MV on days 7 and 14 with highest odds ratios (OR) of MV in neonates with fluid balance ≥ 15%. Peak fluid balance of ≥ 15% was associated with the greatest odds of mortality. Diuretics were used more frequently in neonates with younger GA, smaller birthweight, positive fluid balance, and those on MV. Conclusions: Positive fluid balance negatively impacts pulmonary status. The odds of MV and death increase significantly as peak fluid balance percentage increases in all GA groups. The impact of diuretics on MV and death in preterm neonates needs further evaluation. [ABSTRACT FROM AUTHOR]

The language environment to which children are exposed has an impact on later language abilities as well as on brain development; however, it is unclear how early such impacts emerge. This study investigates the effects of children's early language environment and socioeconomic status (SES) on brain structure in infancy at 6 and 30 months of age (both sexes included). We used magnetic resonance imaging to quantify concentrations of myelin in specific fiber tracts in the brain. Our central question was whether Language Environment Analysis (LENA) measures from in-home recording devices and SES measures of maternal education predicted myelin concentrations over the course of development. Results indicate that 30-month-old children exposed to larger amounts of in-home adult input showed more myelination in the white matter tracts most associated with language. Right hemisphere regions also show an association with SES, with older children from more highly educated mothers and exposed to more adult input, showing greater myelin concentrations in language-related areas. We discuss these results in relation to the current literature and implications for future research. [ABSTRACT FROM AUTHOR]

Tweezer‐type receptors that form π−π stacked supramolecular complexes are important components in functional polymeric materials and molecular machines. Herein, we study how varying specific structural components of tweezer‐receptors impacts their binding. A library of tweezer receptors, each containing two π‐electron poor receptor residues and differing by the nature of the linking unit which was either a flexible 2,2′‐(ethylenedioxy)bis(ethylamine) residue or a rigid 3,3"‐diamino‐m‐terphenyl diamine structure, were synthesised. Each tweezer formed 1 : 1 supramolecular complexes with π‐electron rich residues (1,5‐dihydroxynapthalene and pyrene) as confirmed by UV/Vis and 1H NMR spectroscopic studies. Binding constants were determined to be between 2.3×10−5 and 71 M−1 in organic solvents and were one magnitude greater in aqueous solvents for water soluble systems. The nature of the linker had variable effects on the binding constants, showing the design of tweezer type supramolecular receptors with targeted Ka values is non‐trivial and requires structural optimisation supported by binding constant determination studies. [ABSTRACT FROM AUTHOR]

SUMMARY: The role of mental health review tribunals is to oversee that standards of care and treatment are maintained for involuntary patients and for those on community treatment orders. This article considers some ways in which the basic principles of psychotherapy can be applied by tribunal members to offer patients a sense of hope, encouragement and optimism and reduce the emotional challenge of the tribunal review. [ABSTRACT FROM AUTHOR]

Recently, the oncogenic role of lemur tyrosine kinase 3 (LMTK3) has been well established in different tumor types, highlighting it as a viable therapeutic target. In the present study, using in vitro and cell-based assays coupled with biophysical analyses, we identify a highly selective small molecule LMTK3 inhibitor, namely C36. Biochemical/biophysical and cellular studies revealed that C36 displays a high in vitro selectivity profile and provides notable therapeutic effect when tested in the National Cancer Institute (NCI)-60 cancer cell line panel. We also report the binding affinity between LMTK3 and C36 as demonstrated via microscale thermophoresis (MST). In addition, C36 exhibits a mixed-type inhibition against LMTK3, consistent with the inhibitor overlapping with both the adenosine 5′-triphosphate (ATP)- and substrate-binding sites. Treatment of different breast cancer cell lines with C36 led to decreased proliferation and increased apoptosis, further reinforcing the prospective value of LMTK3 inhibitors for cancer therapy. [ABSTRACT FROM AUTHOR]

Over the last several years, the study of working memory (WM) for simple visual features (e.g., colors, orientations) has been dominated by perspectives that assume items in WM are stored independently of one another. Evidence has revealed, however, systematic biases in WM recall which suggest that items in WM interact during active maintenance. In the present study, we report two experiments that replicate a repulsion bias between metrically similar colors during active storage in WM. We also observed that metrically similar colors were stored with lower resolution than a unique color held actively in mind at the same time. To account for these effects, we report quantitative simulations of two novel neurodynamical models of WM. In both models, the unique behavioral signatures reported here emerge directly from laterally-inhibitory neural interactions that serve to maintain multiple, distinct neural representations throughout the WM delay period. Simulation results show that the full pattern of empirical findings was only obtained with a model that included an elaborated spatial pathway with sequential encoding of memory display items. We discuss implications of our findings for theories of visual working memory more generally. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides (AMPs) are critical to the protection of the urinary tract of humans and other animals from pathogenic microbial invasion. AMPs rapidly destroy pathogens by disrupting microbial membranes and/or augmenting or inhibiting the host immune system through a variety of signaling pathways. We have previously demonstrated that alpha-defensins 1-3 (DEFA1A3) are AMPs expressed in the epithelial cells of the human kidney collecting duct in response to uropathogens. We also demonstrated that DNA copy number variations in the DEFA1A3 locus are associated with UTI and pyelonephritis risk. Because DEFA1A3 is not expressed in mice, we utilized human DEFA1A3 gene transgenic mice (DEFA4/4) to further elucidate the biological relevance of this locus in the murine urinary tract. We demonstrate that the kidney transcriptional and translational expression pattern is similar in humans and the human gene transgenic mouse upon uropathogenic Escherichia coli (UPEC) stimulus in vitro and in vivo. We also demonstrate transgenic human DEFA4/4 gene mice are protected from UTI and pyelonephritis under various UPEC challenges. This study serves as the foundation to start the exploration of manipulating the DEFA1A3 locus and alphadefensins 1-3 expression as a potential therapeutic target for UTIs and other infectious diseases [ABSTRACT FROM AUTHOR]

In this proof-of-concept study, we aim to produce a polyurethane (PU)-based composite that can reduce the amount of viable SARS-CoV-2 virus in contact with the surface of the polymeric film without further interventions such as manual cleaning. Current protocols for maintaining the hygiene of commonly used touchpoints (door handles, light switches, shop counters) typically rely on repeated washing with antimicrobial products. Since the start of the SARS-CoV-2 pandemic, frequent and costly surface sanitization by workers has become standard procedure in many public areas. Therefore, materials that can be retrofitted to touchpoints, yet inhibit pathogen growth for extended time periods are an important target. Herein, we design and synthesise the PU using a one-pot synthetic procedure on a multigram scale from commercial starting materials. The PU forms a robust composite thin film when loaded with 10 wt% silver nanoparticles (AgNPs). The addition of AgNPs increases the ultimate tensile strength, modules of toughness and modulus of elasticity at the cost of a reduced elongation at break when compared to the pristine PU. Comparative biological testing was carried out by the addition of pseudotyped virus (PV) bearing the SARS-CoV-2 beta (B.1.351) VOC spike protein onto the film surfaces of either the pristine PU or the PU nanocomposite. After 24 h without further human intervention the nanocomposite reduced the amount of viable virus by 67% (p = 0.0012) compared to the pristine PU treated under the same conditions. The significance of this reduction in viable virus load caused by our nanocomposite is that PUs form the basis of many commercial paints and coatings. Therefore, we envisage that this work will provide the basis for further progress towards producing a retrofittable surface that can be applied to a wide variety of common touchpoints. [ABSTRACT FROM AUTHOR]

The emergence of several online travel agents (OTA) has come with several benefits for the potential travellers. Many accommodation establishments especially hotels find OTA helpful in this age of technological innovations and are using them as distribution channels for their products. This paper examines why hotel customers opt to book indirectly via OTA rather than making direct booking with the hotel. The paper also determines why hotel customers in the Cape Metropole think it is cheaper and more convenient to make reservations through travel agents. Hotel customer behaviour when booking accommodation is also reviewed to establish the motivations in choosing a specific booking method. Three-hundred hotel guests participated in the study, and the data was analysed descriptively using the IBM Statistical Package for Social Sciences (SPSS). The study revealed a preference for OTAs rather than direct reservation with the hotel, and this was mainly attributed to convenience and affordability. The study is of importance to hotels and OTAs as it advances an understanding of booking behaviours of hotel customers. Recommendations on how hotels could attract and convince customers to book directly to help avoid paying commissions to OTAs were discussed. [ABSTRACT FROM AUTHOR]

Solvent‐free synthesis by using a vibratory ball mill (VBM) offers the chance to access new chemical reactivity, whilst reducing solvent waste and minimising reaction times. Herein, we report the core functionalisation of N,N'‐bis(2‐ethylhexyl)‐2,6‐dibromo‐1,4,5,8‐naphthalenetetracarboxylic acid (Br2‐NDI) by using Suzuki, Sonogashira and Buchwald–Hartwig coupling reactions. The products of these reactions are important building blocks in many areas of organic electronics including organic light‐emitting diodes (OLEDs), organic field‐effect transistors (OFETs) and organic photovoltaic cells (OPVCs). The reactions proceed in as little as 1 h, use commercially available palladium sources (frequently Pd(OAc)2) and are tolerant to air and atmospheric moisture. Furthermore, the real‐world potential of this green VBM protocol is demonstrated by the double Suzuki coupling of a monobromo(NDI) residue to a bis(thiophene) pinacol ester. The resulting dimeric NDI species has been demonstrated to behave as an electron acceptor in functioning OPVCs. [ABSTRACT FROM AUTHOR]

A cheap, conventional, sealed heating reactor proved to be a useful alternative to a microwave reactor in the synthesis of a >20-member MIDA boronate library (MIDA = N-methyliminodiacetic acid). Reaction times were 10 min and work-ups were minimal, saving on energy and solvent usage. [ABSTRACT FROM AUTHOR]

Background: Leprosy is a neglected tropical disease caused by Mycobacterium leprae, leading to disabilities if untreated. The ELISA based on phenolic glycolipid I (PGL-I), or its synthetic version ND-O-BSA, is almost universally positive in multibacillary leprosy and thus extensively used in endemic countries. Household contacts with a positive antibody titer have ~6-fold higher probability to develop the disease than those with a negative titer. Thus, the aim of the study was to evaluate the performance of this ELISA in the setting of a non-endemic country. Methods: We calculate the cut-off using optimized O.D. thresholds, generated by receiver operating characteristics (ROC) curve analysis, testing 39 well-characterized sera obtained from lepromatous leprosy patients with strongly positive ND-O-BSAELISA titer and 39 sera from healthy non-endemic patients never exposed to M. leprae or M. tuberculosis. Indeed, we tested a second set of sera from suspected or confirmed leprosy or household contacts (SLALT group, n=50), and patients with tuberculosis (control group, n=40). Results: We detected 56.4% of SLALT and 22.5% of tuberculosis as positive, consistent with the literature. Conclusion: The ELISA based on ND-O-BSA may thus be considered a good option to be used in a non-endemic area as a screening tool in at risk population usually coming to our center. [ABSTRACT FROM AUTHOR]

NASA's New Horizons mission performed the first flyby of a small Kuiper Belt Object (KBO), (486958) Arrokoth on 1 January 2019. The fast flyby revealed a fascinating, flattened, contact binary replete with a variety of unexpected geologic terrains. However, the irregular shape and constraints imposed by the fast flyby makes it a challenge to understand these features. Here we use the latest New Horizons shape models of Arrokoth to investigate its geophysical environment, including its surface slopes, gravity field, and moments of inertia—which are critical context for understanding Arrokoth's formation, evolution, and peculiar geology. We find that Arrokoth's surface features have a complicated relationship to its geophysical environment. For example, bright material tends to be concentrated in geopotential lows (like the neck), consistent with mass wasting—however, this trend is not consistently observed across Arrokoth. Mass wasting may naturally explain some aspects of Arrokoth's geology, but the actual dynamics of material transport may be complicated owing to Arrokoth's unique shape, spin‐rate, and inferred density. While New Horizons's fast and distant flyby precluded directly measuring Arrokoth's mass, we used techniques previously pioneered for comets and asteroids to infer its density. We find that Arrokoth has a low bulk density of ρ = 235 kg/m3 (1σ range: 155–600 kg/m3). This density is low compared to previously explored small bodies, but is comparable to comets, select binary KBOs, and the ring‐moons of Saturn. This low density may be a critical data‐point for understanding the formation of planetesimals at the dawn of the Solar System. Plain Language Summary: NASA's New Horizons mission performed the first flyby of a small Kuiper Belt Object (KBO), (486958) Arrokoth on 1 January 2019. Arrokoth is a ∼30‐km long, peanut shaped, icy body in the Kuiper Belt—a reservoir of small bodies left over from the Solar System's formation. Arrokoth is the most distant, and likely the least evolved object, ever explored by a spacecraft. Arrokoth's unusual shape makes it challenging to determine how material moves across its surface. We use the latest shape models to calculate Arrokoth's gravity field. Bright material tends to collect in Arrokoth's lowest locations, perhaps indicating material can move downslope. While New Horizons was not able to measure the density of Arrokoth, we are able to infer it using techniques pioneered for studying asteroids and comets. We find that Arrokoth's density is extremely low—more akin to fluffy snow on Earth. If correct, this would be one of the lowest density objects ever explored, closer to the densities of some of the comets and small moons within Saturn's rings. Arrokoth's low density may suggests that the building blocks of planets were assembled very gently in the outer Solar System, in the first few million years of Solar System formation. Key Points: We present new models for the geophysical environment of (486958) Arrokoth based on the latest New Horizons shape modelsMany (but not all) of Arrokoth's enigmatic surface markings are correlated with its geophysical environmentAnalysis of Arrokoth's shape suggests that it has a low density of 235 kg/m3 (1σ range: 155–600 kg/m3) [ABSTRACT FROM AUTHOR]

The New Horizons mission performed a successful flyby of Arrokoth, a distant Kuiper-Belt Object, on January 1, 2019, representing the farthest planetary encounter to date. The navigation strategy and performance required to deliver the spacecraft to the desired flyby target were driven by a number of challenges including those related to Arrokoth's viewing angle and relatively recent discovery in June 2014. These and other challenges required the New Horizons science and navigation teams to devise a strategy in close collaboration that would substantially reduce the flyby navigation errors. Earth-based astrometry and occultation measurements of Arrokoth were collected and used to estimate Arrokoth's orbit and its associated uncertainties, which were in turn used to inform and reduce navigation approach and flyby uncertainties. The New Horizons navigation effort used these a priori orbits along with radio metric and optical navigation measurements to first predict the navigation performance in support of the flyby design, and then estimate New Horizons' trajectory, maneuvers and other filter state parameters during navigation operations. An overview of the Arrokoth orbit estimation and navigation strategy and predicted performance, as well as the operational results from the initial target search campaign in 2004 through Arrokoth's successful flyby in 2019 are presented, along with the principal challenges and most important lessons learned along the way. [ABSTRACT FROM AUTHOR]

The New Horizons spacecraft returned images and compositional data showing that terrains on Pluto span a variety of ages, ranging from relatively ancient, heavily cratered areas to very young surfaces with few-to-no impact craters. One of the regions with very few impact craters is dominated by enormous rises with hummocky flanks. Similar features do not exist anywhere else in the imaged solar system. Here we analyze the geomorphology and composition of the features and conclude this region was resurfaced by cryovolcanic processes, of a type and scale so far unique to Pluto. Creation of this terrain requires multiple eruption sites and a large volume of material (>104 km3) to form what we propose are multiple, several-km-high domes, some of which merge to form more complex planforms. The existence of these massive features suggests Pluto's interior structure and evolution allows for either enhanced retention of heat or more heat overall than was anticipated before New Horizons, which permitted mobilization of water-ice-rich materials late in Pluto's history. Giant icy volcanos (cryovolcanos) on Pluto are unique in the imaged solar system and provide evidence for unexpected, active geology late in Pluto's history. [ABSTRACT FROM AUTHOR]

A key question in early development is how changes in neural systems give rise to changes in infants' behavior. We examine this question by testing predictions of a dynamic field (DF) model of infant spatial attention. We tested 5‐, 7‐, and 10‐month‐old infants in the Infant Orienting With Attention (IOWA) task containing the original non‐competitive cue conditions (when a central stimulus disappeared before a cue onset) and new competitive cue conditions (when a central stimulus remained visible throughout the trial). This allowed testing of five model predictions: (1) that orienting accuracy would be higher and (2) reaction times would be slower for all competitive conditions; (3) that all infants would be slower to orient in the competitive conditions, though (4) older infants would show the strongest competition costs; and (5) that reaction times would be particularly slow for un‐cued competitive conditions. Four of these five predictions were supported, and the remaining prediction was supported in part. We next examined fits of the model to the expanded task. New simulation results reveal close fits to the present findings after parameter modification. Critically, developmental parameters of the model were not altered, providing support for the DF model's account of neuro‐developmental change. [ABSTRACT FROM AUTHOR]

Background: Emergency departments (EDs) often rely on urinalysis (UA) to rapidly identify urinary tract infections (UTIs) in children. However, the suboptimal test characteristics of UA can lead to false-positive results. Novel urinary biomarkers may increase the diagnostic precision of UA. In this study, we compared the concentrations of 6 pre-selected proteins: BH3 interacting domain death agonist (BID), B-cell lymphoma 6 protein, ras GTPase-activating protein 1, cathepsin S (CTSS), 3-hydroxyanthranilate 3,4-dioxygenase, and transgelin-2. Methods: In a pediatric ED, we prospectively enrolled 167 children with UA and urine culture collected. Pyuria was defined as either ≥ 5 white blood cells per high-power field on microscopy or positive leukocyte esterase (LE). The urine culture was considered positive if it yielded ≥ 50,000 colony-forming units per milliliter of any single urinary pathogen. Urine protein levels were measured by enzyme-linked immunosorbent assay and normalized to urine creatinine. Results: BID was significantly higher in the UTI group compared to the culture-negative pyuria group with a mean ratio of 1.42 (95% confidence interval (CI), 1.15, 1.76) when uncorrected for creatinine concentration. When corrected for creatinine concentration, CTSS was significantly elevated in the UTI group compared to the culture-negative pyuria group with a mean ratio of 2.11 (95% CI, 1.39, 3.21). Conclusions: BID and CTSS concentrations were elevated in the urine of children with UTI compared to those with culture-negative pyuria. These proteins deserve further research into their utility to serve as novel biomarkers for UTI. [ABSTRACT FROM AUTHOR]

The current review describes advances in the use of fluorescent 2,1,3‐benzothiadiazole (BTD) derivatives after nearly one decade since the first description of bioimaging experiments using this class of fluorogenic dyes. The review describes the use of BTD‐containing fluorophores applied as, inter alia, bioprobes for imaging cell nuclei, mitochondria, lipid droplets, sensors, markers for proteins and related events, biological processes and activities, lysosomes, plasma membranes, multicellular models, and animals. A number of physicochemical and photophysical properties commonly observed for BTD fluorogenic structures are also described. [ABSTRACT FROM AUTHOR]

Despite over a century of investigations into gullies and gully erosion, the characterization and categorization of gullies and the varied definitions, nomenclatures and terminology used has caused some confusion in understanding and communicating the relationships of gully forms and processes around the world. We firstly review the gully literature and highlight how a lack of consistency in gully definition and characterization prevents unifying theory from being developed within this important field of research, since it is often unclear whether different landscape features being discussed are comparable. We propose that conventionally employed qualitative planform and cross‐sectional characteristics of gullies alone are inadequate to define gully types, yet both these features remain central to most modern gully descriptions. We discuss the need to revise and augment these basic characteristics with clearly defined morphogenetic attributes such as landscape context, soil material characteristics, erosion processes, hydrological integrity, modes of development, and head/side‐wall morphology for an effective, practicable, generic gully classification scheme. Central to a gully classification scheme is the need for a clear definition of what a gully is – and is not – for which geomorphological criteria are proposed to differentiate a 'gully' from other 'incisional land surface forms'. This gully definition hinges largely on the identification of a retreating head scarp and the internal erosion by mass‐movement and other sidewall slope erosion processes, coupled with the transport of the soil materials from the gully void. By defining a gully and synthesizing descriptions of gully 'types' from the literature and our own experience, we propose key morphogenetic attributes of gullies necessary to form a framework for a systematic gully classification scheme. An initial, eclectic classification framework is presented as both a summation and a synthesis of the literature review, and as a progenitor to a dynamic generic classification scheme that is proposed in a follow‐up article. [ABSTRACT FROM AUTHOR]

The orientation and morphology of the bilobate, cold classical Kuiper belt object (486958) Arrokoth (formerly 2014 MU69) is consistent with a slow, tidal merger of a close binary. However, the discrepancy between Arrokoth's present‐day rotation (15.9 hr) and synchronous rotation for nominal cometary densities near ∼500 kg/m3 implies reduction (up to 30%) in post‐merger spin angular momentum. We investigate how collisions with dynamically cold and hot classical Kuiper belt objects might have affected Arrokoth's post‐merger spin. Using a dynamically equivalent triaxial ellipsoid, 5000 Monte Carlo simulations of 100 impacts each, consistent with Arrokoth's cratering record, were carried out. Starting from the assumption of critical, synchronous rotation for a given density, these simulations rarely reproduce Arrokoth's present spin period, unless its true density is near 250 kg/m3. We explore in greater depth the effects of formation of Arrokoth's largest crater (now officially named Sky, previously informally named Maryland). We adopt point‐source scaling and randomly select impact parameters that lead to the crater, using Arrokoth's full bilobate shape. Results from Sky's formation alone are similar to those considering a full range of impactor sizes, unless we adopt low cratering efficiency due to high porosity, which implies substantially larger Sky‐forming impactors. Overall, results imply that the probability of substantial angular momentum change due to impacts alone over Solar System history is unlikely, and spindown from a synchronous, tidal rotation rate to a 15.9‐hr period unlikely unless Arrokoth itself was and is a very low density object (∼250 kg/m3), though we cannot statistically rule out densities up to 400 kg/m3. Plain Language Summary: Both lobes of the cold classical Kuiper belt object Arrokoth were likely in a close spin‐synchronous orbit before they gently merged to form the bilobate body we see today. This spin‐synchronous orbital period depends on density, however, and Arrokoth's observed spin period implies that it either has an extremely low density (much lower than typical cometary values) or underwent significant despinning after the merger. Here we study the spin‐altering effects of impacts by other, small Kuiper belt objects over time and address the likelihood of the required despinning by impacts, with implications for Arrokoth's bulk density. We use a Monte Carlo impact simulation to investigate Arrokoth's rotational response over its impact history, with special attention to the largest recognized crater (Sky). Our results indicate that: (a) Small impacts alone are not capable of altering Arrokoth's spin by much; (b) The likelihood of geophysically significant impact despinning on Arrokoth is low, if it has a typical cometary density of ∼500 kg m−3; (c) Arrokoth's bulk density may actually be quite low, ∼250 kg m−3, implying substantial porosity. Key Points: Impacts of classical Kuiper belt objects consistent with Arrokoth's observed craters caused at best modest spin changesThe formation of the largest craters would have had a larger effect, especially if cratering efficiency is reduced by substantial porosityThe most consistent interpretation of Arrokoth' shape and slow spin is that its bulk density is low, between 250 and 400 kg m−3 [ABSTRACT FROM AUTHOR]